OVERVIEW: What every practitioner needs to know

Are you sure your patient has food allergy? What are the typical findings for this condition?

Food allergies are abnormal immunologic reactions to foods. Most often, food allergies are IgE-mediated and result in immediate development of symptoms that involve a characteristic pathway and characteristic symptoms. Food antigens bind IgE antibodies that are bound to mast cells, which degranulate, releasing histamine and a variety of other mediators. Thus the most common symptoms are related to histamine release, and are the following:

Timing is important in evaluating food allergies

Patients who report that they ate a food and symptoms developed the following day are unlikely to be having an IgE-mediated reaction (since this type of hypersensitivity is immediate). Most often, symptoms will occur in minutes to at most 1 hour later. There are some rarer forms of food allergy that are delayed, such as a recently described allergy to nonprimate mammalian meat (beef, pork, lamb) that may occur 3-5 hours after eating the meat. This type of allergy does not occur with poultry, fish, or shellfish. There are food allergies that are non–IgE mediated and may present hours after ingestion of foods (i.e., food protein–induced enterocolitis syndrome).

Reproducibility is important in evaluating food allergies

Patients who routinely consume a food without any immediate reactions are unlikely to be allergic to that food. The gold standard diagnostic test for food allergies is a double-blind placebo controlled oral food challenge. In practice, often an open food challenge is all that is necessary. Often, patients may say that they "tested positive" for a food on skin testing or with blood tests for food-specific IgEs, but they are able to eat these foods. In this case, the positive test results are likely false.

What other disease/condition shares some of these symptoms?

Conditions that can mimic food allergies include bacterial food poisoning, heavy metal poisoning, scombroid fish ingestion, caffeine, alcohol, foods that may contain histamines, food intolerances (ie, lactose intolerance), pancreatic insufficiency, gallbladder or liver insufficiency, hiatal hernia, gustatory rhinitis, anorexia nervosa, idiosyncratic, and other types of side effects from foods. Patients may have chemically related side effects from foods, such as migraine headaches that are triggered by food chemicals or additives like monosodium glutamate, nitrites, sulfites, and so on.

What caused this disease to develop at this time?

The cause of food allergies is thought to be due to a loss of oral tolerance or a failure to develop tolerance. Immunologic tolerance is the normal process that the body should undergo during development so as not to react to food antigens. When this fails, the body mounts an immunologic response against a variety of food proteins.

The development of tolerance depends on a few important factors: dose and form of the allergen, genetic make-up of the host, normal intestinal flora of the host, and age of the host.

There is current ongoing debate about the optimal age at which to introduce foods to a baby. In the past, the American Academy of Pediatrics had recommended food avoidance until certain ages as a proposed way to reduce food allergies. However, since food allergies have been on a steady rise, this recommendation was changed.

A very important study comparing genetically similar children in Israel and the United Kingdom suggested that introducing peanuts at an earlier age might protect a child from the development of food allergies. Current studies are ongoing and preliminary data has supported that some foods may be more protective if given at earlier ages than previously thought. Until these data are available, it is unclear what the optimal age is for introduction of specific foods. Currently, the standard of care is to recommend introduction of foods when culturally appropriate. It is also recommended that babies should breast-feed exclusively for 4-6 months.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Although the gold standard for diagnosis of food allergies is the double-blind placebo-controlled food challenge, this is not typically necessary in day-to-day clinical practice.

The most important part of making a diagnosis of food allergies is having a good history. Did the patient eat this food for the first time? Was this an immediate reaction that sounded IgE-mediated? Often the suspicion of food allergies is already ruled out by the history when a patient reveals that the food in question has been eaten his/her entire life and he/she has continued to eat it without problems since the reaction occurred. A strong history will often make the diagnosis before a decision is made on testing.

When the history is unclear or not available, testing may be helpful. The two main methods are skin prick testing and serum levels of food-specific IgE levels.

Making the diagnosis of food allergies requires a convincing history in addition to supportive tests. Unfortunately, the positive predictive value of the skin prick test in diagnosing IgE-mediated food allergies is about 50%, which is quite poor. Conversely, the negative predictive value, is about 95%, which is fairly good. Therefore, it is essential to test only the foods that are suspected by the history. Doing skin prick tests for foods that are already tolerated in the diet regularly is not necessary and often may lead to false-positive results.

Would imaging studies be helpful? If so, which ones?

Generally, for food allergies, imaging studies are not necessary.

Confirming the diagnosis

The diagnosis is highly suspected when there is a clear history of an IgE-mediated reaction. Skin testing or specific IgE levels would then confirm this diagnosis. When the history is unclear (e.g., a 1-year-old eats cake for the first time and has a reaction, but the cake contained egg, milk, peanut, and wheat, which the child had never eaten), skin testing may help to confirm a suspicion or rule out the possibility of an allergy. Often a supervised oral food challenge is necessary when there are equivocal test results with an unclear history.

Lastly, if the history is negative for a specific reaction (e.g., a patient experiences migraine headaches each time she has Chinese food containing MSG but she eats all of the same foods without symptoms when they do not contain MSG), doing testing is not necessary and may cause more confusion if false-positive results occur. In this case, it would be important to counsel the patient on food chemical/additive side effects and the differences between this and allergic reactions.

If you are able to confirm that the patient has food allergies, what treatment should be initiated?

It is essential to provide counseling on appropriate food avoidance. To do so, one must be very convinced about the diagnosis, since strict food avoidance is often very difficult on patients' families. Recommending unnecessary food avoidance only decreases a patient's quality of life and may cause malnutrition, so it is very important to make the diagnosis correctly.

Currently, the accepted standard of care dictates strict avoidance of the offending food and preparation for an accidental allergic reaction by having rescue medications readily available. These rescue medications include an antihistamine (such as diphenhydramine) for mild reactions and injectable epinephrine for severe reactions.

Patients should be counseled on when to use the epinephrine and when to use the antihistamine. A food allergy action plan should be given to all patients so that they have an understanding of when they should use which medications. If epinephrine is used, emergency medical services should be contacted and the patient should be observed at an emergency department.

There is no active treatment currently available to desensitize patients or induce tolerance, but there are many therapies that are under investigation at several institutions around the world. These include, but are not limited to, oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, a monoclonal anti-IgE antibody (omalizumab), a Chinese herbal medication, modified food allergens, and highly heated milk or eggs for patients who are allergic to milk and eggs. There are many emerging therapies that have great promise to hopefully be an active disease-modifying therapy for food allergies.

What are the adverse effects associated with each treatment option?

Use of epinephrine in patients with coronary artery disease may induce cardiac ischemia from a suddenly elevated heart rate. Therefore, use in the elderly should be quite conservative and patients need to be careful that they are definitely needing the medication. It is fairly well tolerated in children. Antihistamines are fairly well tolerated, but may cause drowsiness.

What are the possible outcomes of food allergies?

Depending on which food a patient is allergic to, there may be a good chance of "outgrowing" the food allergy or developing tolerance. This is most true with foods like milk, eggs, wheat, and soy. In contrast, peanut and tree nut allergies, as well as allergies to fish and shellfish, the likelihood of spontaneously outgrowing the food allergy is much lower. For peanut allergies, it is estimated that about 80% of patients continue to have persistent food allergy for life, which means that about 20% of patients could "outgrow" their allergies.

What causes this disease and how frequent is it?

The actual cause of food allergies is not known, but the pathogenesis is thought to be due to a loss of oral tolerance or a failure of oral tolerance to develop for specific food antigens. The normal immunologic response of the body to food antigens in the gastrointestinal (GI) tract in developing infants is not to develop an immunologic response against what should be "innocent" antigens.

The GI tract is the largest immunologic organ in the body, with continued exposure to the environment over a large surface area of its epithelial layer. Tremendous amounts of food proteins come into contact with immune cells, and normally these cells do not develop any response to the food proteins. However, food allergies develop when they fail to remain inert.

Food allergies have become increasingly prevalent over the past 20 years in developed countries. It is estimated that about 6%-8% of children younger than age 4 years and about 4% of Americans older than 10 years of age are affected by food allergies. Food allergies are also the most common cause of anaphylaxis seen in the emergency department.

Among children, the most common foods involved are milk, egg, peanuts, tree nuts, wheat, and soy.

Among adults, the most common foods involved are peanuts, tree nuts, fish, and shellfish. Adults also may commonly have allergies to fruits and vegetables (this is quite often a type of food allergies called oral allergy syndrome).

There is no known genetic defect that is clearly associated with food allergies alone, although there are some known genetic syndromes that are associated with food allergies (i.e., Foxp3 mutation in patients causes a disorder called IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome, which presents with food allergies). For food allergies themselves (not as part of a syndrome), there is no specific gene defect. Recent data suggest that mutations in a gene called filaggrin are associated with atopic disorders, including food allergies, eczema, and asthma. What is known, though, is that a family history of atopy is a risk factor for food allergies (as are all other atopic disorders such as eczema, asthma, or allergic rhinitis).

How do these pathogens/genes/exposures cause the disease?

This disease is not caused by a pathogen or known genetic defect or exposure.

Other clinical manifestations that might help with diagnosis and management

A special population of patients might not present with immediate IgE-mediated symptoms. This special population is generally very young infants or babies who are breast-fed and may be receiving small amounts of food allergen through breast milk or possibly very small amounts of a food allergen (i.e., milk protein) through a formula or other food product.

These patients may present with severe eczema that is not amenable to standard dermatologic therapies. Removal of the food allergen from their diet may greatly improve their eczema. However, for a majority of patients with mild to moderate eczema, it is not likely that food allergens are responsible for the skin disease.

What complications might you expect from the disease or treatment of the disease?

There is a risk for anaphylaxis, a severe allergic reaction with exposure to the known antigen. Death or major morbidity may occur from laryngeal edema or shock, or other life-threatening symptoms may be seen such as severe asthma exacerbation.

Are additional laboratory studies available; even some that are not widely available?

Currently, the most helpful laboratory studies include skin prick tests and serum levels of food-specific IgE. Some laboratory tests that are not widely available are offered to patients but are not clinically validated or have been shown to be unhelpful in the diagnosis of food allergies. Most often these other types of tests are being recommended by alternative practitioners and nonspecialists. These tests could include chiropractic laser diagnosis, food-specific IgG levels, basophil histamine release/activation, hair analysis, applied kinesiology, mediator release assay (LEAP [lifestyle, eating and performance] diet), electrodermal testing, ALCAT (antigen leukocyte cellular antibody test), and ELISA/ACT tests.

How can food allergies be prevented?

Currently there is no known method to prevent food allergies. A considerable amount of debate has been raised about whether or not to limit the maternal diet during pregnancy and laction. A recent food allergy guideline sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) was released in 2010 with specific recommendations not to restrict the maternal diet during pregnancy or lactation as a way to prevent the development of food allergies.

This same expert panel did recommend exclusive breast-feeding through 4-6 months of age, not because there is any evidence that it may prevent atopy but because of the other general benefits associated with breast-feeding. There was also no recommendation for using soy formula in place of cow's milk–based formula as a way to prevent food allergies. They did suggest the use of hydrolyzed infant formulas in "at risk" patients who were not being exclusively breast-fed.

Lastly, the age at which food allergens are introduced has been a subject of great debate as well. The expert panel suggested that the introduction of solid foods not be delayed beyond 4-6 months of age and noted that potentially allergenic foods could be introduced at that time as well.

What is the evidence?

It is well understood that strict avoidance of food allergens is the best way to prevent reactions to foods once the diagnosis has been made. Treatment of acute reactions with antihistamines and injectable epinephrine is also well established. The areas that have a lack of adequate evidence include the current understanding of how to prevent the development of food allergies in patients at risk for atopy as well as in the general population.

Evidence is still necessary and being generated for future therapies that may have a disease-modifying or curative effect (oral immunotherapy, sublingual immunotherapy, epicutaneous immunotherapy, Chinese herbal medications, and others).

A great resource is the guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAID-sponsored expert panel, which was published in December 2010 in the Journal of Allergy and Clinical Immunology:

Ongoing controversies regarding etiology, diagnosis, treatment

As mentioned above, there are controversies and debate among specialists in our understanding of how to prevent food allergies from a dietary standpoint in the maternal diet and in the young patient. Since the current treatment is still avoidance, there is no great debate about therapeutic options (which are not available to the general public, but are currently being studied).